Scientific Opinion on the re-evaluation of cochineal, carminic acid, carmines (E 120) as a food additive

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Article
Panel on Food Additives and Nutrient Sources Added to Food
EFSA Journal
EFSA Journal 2015;13(11):4288 [66 pp.].
doi
10.2903/j.efsa.2015.4288
Panel members at the time of adoption
Fernando Aguilar, Riccardo Crebelli, Alessandro Di Domenico, Birgit Dusemund, Maria Jose Frutos, Pierre Galtier, David Gott, Ursula Gundert-Remy, Claude Lambré, Jean-Charles Leblanc, Oliver Lindtner, Peter Moldeus, Alicja Mortensen, Pasquale Mosesso, Agneta Oskarsson, Dominique Parent-Massin, Ivan Stankovic, Ine Waalkens-Berendsen, Rudolf Antonius Woutersen, Matthew Wright and Younes Maged.
Acknowledgements

The Panel wishes to thank the members of the former Working Group ‘A’ Food Additives and Nutrient Sources (2011–2014) and the Standing Working Group on the re-evaluation of food colours: Fernando Aguilar, Riccardo Crebelli, Alessandro Di Domenico, Maria Jose Frutos, Pierre Galtier, David Gott, Claude Lambré, Jean-Charles Leblanc, Agneta Oskarsson, Jeanne Stadler, Paul Tobback, Ine Waalkens-Berendsen and Rudolf Antonius Woutersen, for the preparatory work on this scientific opinion and EFSA staff members Petra Gergelova, Ana Maria Rincon and Stavroula Tasiopoulou for the support provided to this scientific opinion. The ANS Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output.

Contact
Type
Opinion of the Scientific Committee/Scientific Panel
On request from
European Commission
Question Number
EFSA-Q-2011-00360
Adopted
27 October 2015
Published
18 November 2015
Affiliation
European Food Safety Authority (EFSA), Parma, Italy
Note
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Abstract

Cochineal, carminic acid, carmines (E 120) have been previously evaluated by JECFA and by the SCF. Both committees established an ADI of 5 mg/kg bw/day. The Panel noted that the title of the EC specifications for E 120 does not adequately correspond to the specified food additive and therefore, proposes to modify it to “E 120 cochineal extract, carminic acid and carmines”, which would more accurately reflect the material used. The Panel also noted that the specifications need to be updated with regard to the maximum limits for certain toxic elements present as impurities, to ensure that E 120 will not be a significant source of exposure to these toxic elements in food. No ADME studies on cochineal extract, carminic acid or carmines were available for evaluation, but indirect evidence suggests that carmines are absorbed and distributed in the body. Acute, short-term, subchronic, carcinogenicity, reproduction and developmental toxicity studies conducted in rats or mice did not show toxicological potential. Consideration of the available information regarding genotoxicity indicated that carminic acid is not genotoxic. The Panel concluded that the present dataset does not give reason to revise the ADI of 5 mg carmine (containing approximately 50 % carminic acid)/kg bw, allocated by the SCF in 1983. The Panel concluded that this ADI should be expressed as carminic acid content, which would correspond to 2.5 mg carminic acid/kg bw/day. The Panel considered that, since no threshold dose can be established for allergic reactions, it is advisable that exposure to the eliciting allergens, such as proteinaceous compounds, in E 120 is avoided by introducing appropriate purification steps in the manufacturing process. Refined exposure estimates show that exposure to E 120 for the non-brand-loyal scenario, is below the ADI of 2.5 mg carminic acid/kg bw/day for all population groups.

Summary

Following a request from the European Commission (EC), the Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion re-evaluating the safety of cochineal, carminic acid, carmines (E 120) as a food additive.

The Panel was not provided with a newly submitted dossier and based its evaluation on previous evaluations, additional literature that became available since then and the information available following public calls for data. The Panel noted that not all original studies on which previous evaluations were based were available for re-evaluation by the Panel. To assist in identifying any emerging issue or any information relevant for the risk assessment, EFSA outsourced a contract to deliver an updated literature review on toxicological endpoints, dietary exposure and occurrence levels of cochineal extract, carminic acid and carmines (E 120), which covered the period from the beginning of 2013 up to the end of 2014. Further updates have been performed by the Panel.

Cochineal, carminic acid and carmines (E 120) are red anthraquinone dyes authorised as food additives in the European Union (EU), in accordance with Annex II to Regulation (EC) No 1333/2008.

Cochineal, carminic acid and carmine (E 120) have most recently been evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 2000, which set new specifications, and by the Scientific Committee for Food (SCF) in 1983. Both committees established an Acceptable Daily Intake (ADI) of 5 mg/kg body weight (bw)/day. The JECFA ADI, established in 1982 for carmines (formerly cochineal, carmines and carminic acid), includes ammonium carmine or the equivalent calcium, potassium or sodium salts. For the SCF, the ADI applies to cochineal (carmines), without further details being specified. The 1981 JECFA evaluation specifically excluded the lithium salt, considering it as not acceptable for food additive use.

Specifications have been defined in Commission Regulation (EU) No 231/2012 and by JECFA in 2000. In the EC specifications, cochineal, carminic acid and carmine colours are defined as having not less than 2.0 % carminic acid in the extracts and not less than 50 % carminic acid in the chelates. The remaining material (50 to 80 %) is not precisely specified, being only described as cations that may be present in excess in the colour and also maybe containing proteinaceous material derived from the source insect, together with free carminate or a small residue of unbound aluminium cations. The Panel noted thus that the specifications of carmines need to be updated with respect to the percentage of material not accounted for. The Panel noted that the title of the EC specifications, “E 120, cochineal, carminic acid, carmines”, does not adequately correspond to the specified food colour. The Panel also noted that the actual EC specifications for cochineal extract, carminic acid, carmines do not include limits for the protein content, total ash, residual solvents, or insoluble matter. The Panel considered that further indication on the proportions or percentages of these components, particularly the protein content and the molecular weight of the key allergenic proteins, in the commercial product should be required. Furthermore, the Panel considered that the maximum limits for toxic elements (arsenic, lead, mercury and cadmium) present as impurities in the EC specifications for E 120 should be revised in order to ensure that E 120 used as a food additive will not be a significant source of exposure to these toxic elements in food.

The Panel noted that the term Cochineal per se is a description of the ground bodies of the female insect Dactylopius coccus Costa before extraction, and to the knowledge of the Panel, this material is not used as a food colour. Furthermore, the composition of cochineal extracts is not well defined, and, as described further, the established ADI was based on studies using carmine with a defined amount of carminic acid as test material. Therefore, the Panel proposes that the current title of the food additive (“E 120 cochineal, carminic acid, carmines”) should be revised to “E 120 cochineal extract, carminic acid and carmines” which would more accurately reflect the material used. Carmines should meet existing carmines EC specifications including those concerning the content of ≥ 50 % carminic acid.

No studies on absorption, distribution, metabolism or excretion of cochineal extract, carminic acid or carmines were available for this evaluation. However, both the ionisation properties of carminic acid and indirect evidence from toxicological studies suggest that these compounds can be absorbed to some extent as suggested by the accumulation of colour in tissues and the red colouring of urine reported in rats treated with ammonium carmine.

Short-term and subchronic studies conducted in rats and mice did not show toxicological potential.

Two long-term studies in rats and mice investigated the carcinogenic potential of carmine and cochineal extract, respectively. The rat study on carmine reported significantly higher incidences of acinar hyperplasia and duct ectasia of the mammary tissue in female rats given carmines, at all doses, compared with controls. The mammary hyperplasia seen in the rat study was not reported in the mouse study performed with cochineal extract, and the general pattern of tumour incidence in the mouse study was not significantly different from that of the controls. After considering all the available information, the Panel considered that the incidences of mammary hyperplasia reported in the rat study were not treatment related. Overall, the Panel concluded that carmine is not carcinogenic.

No adverse effects were reported in reproductive and developmental toxicity studies in rats and mice when tested at doses of up to 1 000 mg carmine/kg bw/day or 3 000 mg cochineal extract/kg bw/day. Overall, the Panel considered that the available data suggest that cochineal extract and carmine do not show reproductive or developmental toxicity.

The available information regarding genotoxicity indicates that carminic acid is not genotoxic, and, by read-across, carmine is also considered non-genotoxic.

The Panel concluded that the present dataset does not give reason to revise the ADI of 5 mg carmine (containing approximately 50 % carminic acid)/kg bw allocated by the SCF in 1983, but considered that for clarification this ADI should only apply to cochineal extract and to carmine. The Panel concluded that this ADI should be expressed as carminic acid content, and this would correspond to 2.5 mg carminic acid/kg bw/day.

The Panel noted that the composition of cochineal tested in the toxicological studies available is not well defined and that, to the knowledge of the Panel, Cochineal (the ground bodies of the female insect D. coccus Costa before extraction) is not used as a food colour in the EU. Furthermore, taking into account that the ADI was derived from toxicological studies using carmine as test material with defined amounts of carminic acid (46 to 56 % carminic acid), which match those specified in the EU specifications, the Panel concluded that based on available information, the ADI of 5 mg/kg bw/day does not apply to Cochineal (the ground bodies of the female insect). Lithium salts of carminic acid are not covered by this ADI.

Using the “maximum level exposure assessment scenario”, the mean exposure to E 120 from its use as a food additive ranged from 0.1 mg/kg bw/day in infants to 3.9 mg/kg bw/day in toddlers, while the high exposure using this scenario ranged from 0.3 mg/kg bw/day in infants to 6.7 mg/kg bw/day in toddlers.

Using the refined brand-loyal exposure assessment scenario, the mean exposure to E 120 from its use as a food additive ranged from 0.1 mg/kg bw/day in infants, adolescents, adults and the elderly to 2.1 mg/kg bw/day in toddlers. The high exposure to E 120 using this scenario ranged from 0.2 mg/kg bw/day in the elderly to 4.7 mg/kg bw/day in toddlers.

Using the refined non-brand-loyal exposure assessment scenario, the mean exposure to E 120 from its use as a food additive ranged from 0.02 mg/kg bw/day in infants to 0.6 mg/kg bw/day in toddlers. The high exposure to carminic acid, carmines (E 120) from its use as food additive using this scenario ranged from 0.1 mg/kg bw/day in infants, adolescents, adults and the elderly to 1.1 mg/kg bw/day in toddlers.

Overall, refined exposure estimates for the non-brand-loyal scenario for infants, toddlers, children adolescents, adults and the elderly show that exposure to E 120 is below the ADI of 2.5 mg carminic acid/kg bw/day for all population groups.

The Panel considered that the ADI of 5 mg/kg bw/day does not cover minimum sensitising or eliciting doses for susceptible individuals. Allergic reactions have been associated with exposure to cochineal extract and carmines. Both substances are able to trigger acute hypersensitivity reactions, such as Quincke’s oedema, dyspnoea and bronchospasm, in sensitised individuals, and can cause severe anaphylactic reactions. In addition, chronic hypersensitivity symptoms, such as rhinoconjuctivitis and asthma, have also been associated with occupational exposure to carmine. The reported effects are likely to be the consequence of allergic reactions involving an immunoglobulin E (IgE)-mediated mechanism, elicited by proteinaceous compounds in the food colour E 120.

The Panel noted that cases of severe allergic reactions, occurring after the consumption of carmine-containing foodstuffs, have been reported, and indicated that the information provided to alert individuals allergic to these colours is not sufficiently acted upon. The Panel considered that, since no threshold dose can be established for allergic reactions, it is advisable that exposure to the eliciting allergens, such as proteinaceous compounds, is avoided as much as possible. Therefore, the Panel considered that it may be advisable to reduce the presence of these allergens as much as possible by introducing appropriate purification steps to the manufacturing process.

Keywords
Cochineal extract, carminic acid, carmines, E 120, CI Natural Red 4, INS No 120, 7-β-D-glucopyranosyl-3,5,6,8-tetrahydroxy-1-methyl-9,10-dioxoanthracene-2-carboxylic acid
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